When heterologous genes are expressed in large amounts in bacteria or the like by means of recombinant DNA techniques, the produced protein may be obtained in an insoluble form (inclusion bodies). In addition, when a protein is chemically modified, there may be some cases where aggregation also takes place between the proteins, to form insoluble aggregates. When a protein is purified from the protein in an insoluble form, there is generally employed a process comprising the steps of once solubilizing inclusion bodies or aggregates by using a denaturing agent, and thereafter removing the denaturing agent by dialysis to give a protein solution.
However, in the process described above, a major part of the desired protein has been subjected to re-aggregation during dialysis to form insoluble aggregates. Since the formation of aggregates during the dialysis as described above can be a factor for lowering a recovery rate of a soluble protein, a process for suppressing aggregation of the protein has been desired.
Accordingly, a first object of the present invention is to provide a process for recovering a soluble protein having a higher recovery rate by suppressing the aggregation of the protein when a denaturing agent is removed from the solubilization treatment solution containing a solubilized protein. Further, a second object of the present invention is to provide a process for removing a denaturing agent from the above solubilization treatment solution in which the aggregation of the protein is suppressed. These objects and other objects of the present invention will be apparent from the following description.